6-(6-hexyloxy)-9H-purine | 62134-31-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 6-(6-hexyloxy)-9H-purine
• 英文别名: 6-(hexyloxy)purine；6-hexyloxypurine；6-hexyloxypyrine；1H-Purine, 6-(hexyloxy)-；6-hexoxy-7H-purine
• CAS: 62134-31-0
• 化学式: C₁₁H₁₆N₄O
• 分子量: 220.274
• InChiKey: FBFLBIMNHQJMBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  16
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  63.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2',3'-二脱氧胸苷 、 6-(6-hexyloxy)-9H-purine 在 对硝基苯酚 、 potassium phosphate buffer containing 0.004percent potassium azide (buffer A) 、 TPase 作用下， 反应 7.5h， 以34%的产率得到6-(hexyloxy)-9-<(2R,5S)-tetrahydro-5-(hydroxymethyl)-2-furyl>-9H-purine
  参考文献：
  名称：

  Novel 6-alkoxypurine 2',3'-dideoxynucleosides as inhibitors of the cytopathic effect of the human immunodeficiency virus

  摘要：

  Twenty-one 6-alkoxypurine 2',3'-dideoxynucleosides were enzymatically synthesized with nucleoside phosphorylases purified from E. coli. Eighteen analogs exhibited anti-HIV-1 activity in MT4 cells. Two analogs,6-(hexyloxy)-(17) and 6-(heptyloxy)-(18) purine 2',3'-dideoxynucleoside, were as potent as 2',3'-dideoxyinosine (ddI, didanosine, Videx). Although the antiviral activities of 17 and 18 were equivalent, 18 was more cytotoxic. Analogs containing less than four carbons in the 6-alkoxypurine substituent exhibited weak anti-HIV-1 activity. Analogs containing more than seven carbons in the 6-alkoxypurine substituent were too cytotoxic to be effectively evaluated for antiviral activity. Several 6-alkoxypurine 2',3'-dideoxynucleosides were evaluated for substrate activity with calf intestinal adenosine deaminase (ADA). Increasing the carbon chain length of the 6-alkoxypurine substituent decreased the rate of dealkoxylation. The best substrate in this series was 6-methoxypurine 2',3'-dideoxynucleoside (1); however, the rate of dealkoxylation of 100 muM 1 was 0.17 % of the rate of deamination of 100 muM 2',3'-dideoxyadenosine. Compound 17, the most potent anti-HIV-1 analog, was not a substrate for ADA. EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), a potent inhibitor of ADA, had little effect on the antiviral activities of 17 and ddI. In contrast, coformycin, a potent inhibitor of both ADA and AMP deaminase, dramatically decreased the antiviral activity of 17, but not the antiviral activity of ddI. Thus, AMP deaminase appeared to be involved in the anabolism of 17. The pharmacokinetic profile of 17, the most promising analog in this series, was determined in the rat. At least seventeen metabolites of 17, including ddI, were detected in plasma samples. This analog also had poor oral bioavailability.

  DOI：

  10.1021/jm00055a009
• 作为产物：
  描述：

  6-氯嘌呤 、 正己醇 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 26.0h， 以90%的产率得到6-(6-hexyloxy)-9H-purine
  参考文献：
  名称：

  新型双脱氧核苷的光化学合成。

  摘要：

  从普通的环丁酮前体的光化学扩环制备了一系列基于api糖家族的2'，3'-二脱氧核苷。起始酮，（+/-）3- [2'-（苯甲酰氧基）乙基] -2，2-二甲基环丁酮（12）由市售的（+/-）α-pine烯制备。由于光学纯的α-the烯的对映体也可商购，因此可以使用相同的方法光学纯地制备这些核苷。

  DOI：

  10.1081/ncn-100002080

文献信息

• Synthesis and HIV Inhibition Activity of 2‘,3‘-Dideoxy-3‘-<i>C</i>-hydroxymethyl Nucleosides
  作者：E. Lee-Ruff、Mario Ostrowski、Azim Ladha、Dennis V. Stynes、Isaak Vernik、Ji-Long Jiang、Wei-Qin Wan、Shi-Fa Ding、Sadhna Joshi

  DOI：10.1021/jm950822k

  日期：1996.1.1

  A series if 2',3'-dideoxy-3'-C-hydroxymethyl purine nucleosides were prepared based on the photochemical ring expansion of a chiral cyclobutanone precursor, (2S)-trans-2,3-bis[(benzoyloxy)methyl]cyclobutanone, in the presence of a 6-substituted purine. Both alpha- and beta-anomers are produced in this transformation. Deprotection was effected by reaction of the photoadducts with saturated methanolic

  基于手性环丁酮前体（2S）-反式2,3-双[（苯甲酰氧基）甲基]的光化学扩环，制备了一系列2'，3'-二脱氧-3'-C-羟甲基嘌呤核苷环丁酮，在6-取代的嘌呤存在下。在这种转化中，α-和β-端基异构体均产生。通过光加合物与饱和甲醇氨的反应进行脱保护。测试了九种嘌呤核苷对HIV IIIB病毒对H9细胞的抑制作用。6-己氧基和腺嘌呤衍生物4e，c似乎在抑制病毒繁殖方面最有效，而4c的活性与ddI和AZT相当。
• Enantioselective Preparation of 2‘,3‘-Dideoxynucleosides and Their Analogues from Ring-Expansion of Cyclobutanones. 2. Synthesis of 2‘,3‘-Dideoxyribosides and (1<i>S</i>,3<i>R</i>)-1- Amino-3-(hydroxymethyl)cyclopentane¹
  作者：Edward Lee-Ruff、Feng-de Xi、Jiang Hua Qie

  DOI：10.1021/jo9517151

  日期：1996.1.1
• US5580973A
  申请人：——

  公开号：US5580973A

  公开（公告）日：1996-12-03
• Novel 6-alkoxypurine 2',3'-dideoxynucleosides as inhibitors of the cytopathic effect of the human immunodeficiency virus
  作者：Charlene L. Burns、Marty H. St. Clair、Lloyd W. Frick、Thomas Spector、Devron R. Averett、Michael L. English、Timothy J. Holmes、Thomas A. Krenitsky、George W. Koszalka

  DOI：10.1021/jm00055a009

  日期：1993.2

  Twenty-one 6-alkoxypurine 2',3'-dideoxynucleosides were enzymatically synthesized with nucleoside phosphorylases purified from E. coli. Eighteen analogs exhibited anti-HIV-1 activity in MT4 cells. Two analogs,6-(hexyloxy)-(17) and 6-(heptyloxy)-(18) purine 2',3'-dideoxynucleoside, were as potent as 2',3'-dideoxyinosine (ddI, didanosine, Videx). Although the antiviral activities of 17 and 18 were equivalent, 18 was more cytotoxic. Analogs containing less than four carbons in the 6-alkoxypurine substituent exhibited weak anti-HIV-1 activity. Analogs containing more than seven carbons in the 6-alkoxypurine substituent were too cytotoxic to be effectively evaluated for antiviral activity. Several 6-alkoxypurine 2',3'-dideoxynucleosides were evaluated for substrate activity with calf intestinal adenosine deaminase (ADA). Increasing the carbon chain length of the 6-alkoxypurine substituent decreased the rate of dealkoxylation. The best substrate in this series was 6-methoxypurine 2',3'-dideoxynucleoside (1); however, the rate of dealkoxylation of 100 muM 1 was 0.17 % of the rate of deamination of 100 muM 2',3'-dideoxyadenosine. Compound 17, the most potent anti-HIV-1 analog, was not a substrate for ADA. EHNA (erythro-9-(2-hydroxy-3-nonyl) adenine), a potent inhibitor of ADA, had little effect on the antiviral activities of 17 and ddI. In contrast, coformycin, a potent inhibitor of both ADA and AMP deaminase, dramatically decreased the antiviral activity of 17, but not the antiviral activity of ddI. Thus, AMP deaminase appeared to be involved in the anabolism of 17. The pharmacokinetic profile of 17, the most promising analog in this series, was determined in the rat. At least seventeen metabolites of 17, including ddI, were detected in plasma samples. This analog also had poor oral bioavailability.
• PHOTOCHEMICAL SYNTHESIS OF NOVEL DIDEOXYNUCLEOSIDES
  作者：E. Lee-Ruff、R. Margau

  DOI：10.1081/ncn-100002080

  日期：2001.2.28

  A series of 2',3'-dideoxynucleosides based on the apiose family was prepared from photochemical ring-expansion of a common cyclobutanone precursor. The starting ketone, (+/-) 3-[2'-(benzoyloxy)ethyl]-2,2-dimethylcyclobutanone (12) was prepared from commercially available (+/-)alpha-pinene. Since the optically pure antipodes of alpha-pinene are also commercially available, these nucleosides can be prepared

  从普通的环丁酮前体的光化学扩环制备了一系列基于api糖家族的2'，3'-二脱氧核苷。起始酮，（+/-）3- [2'-（苯甲酰氧基）乙基] -2，2-二甲基环丁酮（12）由市售的（+/-）α-pine烯制备。由于光学纯的α-the烯的对映体也可商购，因此可以使用相同的方法光学纯地制备这些核苷。